1. Field of the Invention
The present invention relates generally to osmotic delivery systems for delivering beneficial agents, and more particularly, to osmotic delivery system semipermeable body assemblies which control the delivery rate of a beneficial agent from an osmotic delivery system incorporating one of the semipermeable body assemblies.
2. Description of the Related Art
Controlled delivery of beneficial agents, such as drugs, in the medical and veterinary fields has been accomplished by a variety of methods. One method for controlled prolonged delivery of beneficial agents involves the use of osmotic delivery systems. These devices can be implanted to release beneficial agents in a controlled manner over a preselected time or administration period. In general, osmotic delivery systems operate by imbibing liquid from the outside environment and releasing corresponding amounts of the beneficial agent.
FIG. 1 illustrates a cross-sectional view of a known osmotic delivery system 20. The osmotic delivery system 20, commonly referred to as an “osmotic pump,” generally includes some type of a capsule or enclosure 22 having a semipermeable portion which may selectively pass water into an interior of the capsule which contains a water-attracting osmotic agent 24. In the known osmotic delivery system illustrated in FIG. 1, the walls of the capsule 22 are substantially impermeable to items within and outside the capsule, and the plug 26 acts as the semipermeable portion. The difference in osmolarity between the water-attracting agent 24 and the exterior of the capsule causes water to pass through the semipermeable portion of the capsule which in turn causes the beneficial agent 23 to be delivered from the capsule 22 through the delivery port 29. The water-attracting agent 24 may be the beneficial agent delivered to the patient; however, in most cases such as that illustrated in FIG. 1, a separate osmotic agent is used specifically for its ability to draw water into the capsule 22.
When a separate osmotic agent 24 is used, the osmotic agent may be separated from the beneficial agent 23 within the capsule 22 by a movable dividing member or piston 28. The structure of the capsule 22 is such that the capsule does not expand when the osmotic agent 24 takes in water and expands. As the osmotic agent 24 expands, it causes the beneficial agent 23 to be discharged through the delivery port 29 at the same rate as the liquid, which is typically water, enters the osmotic agent 24 by osmosis. Osmotic delivery systems may be designed to deliver a beneficial agent at a controlled constant rate, a varying rate, or in a pulsatile manner.
In the known osmotic delivery system 20 illustrated in FIG. 1, an osmotic tablet is used as the osmotic agent 24 and is placed inside the capsule 22. The membrane plug 26 is placed in an opening in the capsule 22 through which the osmotic agent 24 and piston 28 were inserted. Known membrane plugs 26 are typically a cylindrical member with ribs, and operate in the same manner as a cork. These membrane plugs 26 seal the interior of the capsule from the exterior environment, essentially permitting only certain liquid molecules from the environment of use to permeate through the membrane plug into the interior of the capsule 22. The rate that the liquid permeates through the membrane plug 26 controls the rate at which the osmotic agent 24 expands and drives a desired concentration of beneficial agent 23 from the osmotic delivery system 20 through the delivery port 29. The rate of delivery of the beneficial agent from the osmotic delivery system 20 may be controlled by varying the permeability coefficient of the membrane plug 26.
By varying the permeability coefficient of the membrane plug 26, the liquid permeation rate through the membrane is controlled. Osmotic delivery systems requiring a high beneficial agent delivery rate typically use membrane plugs having high permeability coefficients. Osmotic delivery systems requiring a low beneficial agent delivery rate use membrane plugs having low permeability coefficients. The permeability coefficient is dependent on the particular material or combination of materials used in each membrane plug 26. Thus, the known osmotic delivery system 20 illustrated in FIG. 1, which includes a membrane plug 26, may control the delivery rate of the beneficial agent 23 by forming the same configuration plug 26 from different semipermeable materials having permeability coefficients corresponding to the desired beneficial agent delivery rate. One problem associated with obtaining different permeation rates in this manner is that a different membrane material must be used for every system which has a different desired beneficial agent delivery rate, requiring the purchase of many different membrane materials and manufacture of many different membrane plugs 26.
Although the osmotic delivery device illustrated in FIG. 1 delivers consistent and reproducible beneficial agent delivery rates, it is not possible to easily alter the beneficial agent release rate from the osmotic delivery device; a new membrane plug must be manufactured and incorporated into the device for each application. In many instances, it is desirable to easily increase or decrease the beneficial agent release rate from the osmotic delivery device. For example, the release rate for some drugs should be increased or decreased for osmotic delivery devices that are to be implanted if the patient is overweight or underweight. Additionally, many disease treatment regimens require dose titration to optimize therapeutic response to the beneficial agent, requiring that the beneficial agent release rate be adjusted in accordance with the patient's efficacious response. It is not possible to easily adjust the beneficial agent release rate from current osmotic delivery devices, such as that illustrated in FIG. 1.
Many osmotic delivery systems which use membrane plugs, such as that illustrated in FIG. 1, must administer beneficial agents at rapid delivery rates over a short period of time. These known systems use membrane materials having high permeability coefficients, i.e., high liquid uptake semipermeable materials. In general, high liquid uptake semipermeable materials are those that have greater than 60% water uptake, where % water uptake=100×(wet weight−dry weight)/dry weight. Thus, low uptake semipermeable materials have equal or less than 60% water uptake.
A dramatic problem associated with membrane plugs made from high liquid uptake semipermeable materials is that the membrane plug material has a tendency to absorb liquid and swell as the liquid from the surrounding environment permeates through the membrane. This is problematic because when the membrane plug overly swells, it exerts forces on the walls of the enclosure. Such forces may rupture the enclosure and allow the beneficial agent, osmotic agent or other items within the interior of the enclosure to escape to the environment of use. Furthermore, the membrane plug may become dislodged from the system, which is especially hazardous with implantable delivery systems. Because of biocompatibility and delivery rate considerations, high liquid uptake membrane materials often must be used in osmotic delivery systems destined for human implantation; consequently, there is a need for osmotic delivery systems having membrane plugs which remain intact in the capsule during all phases of delivery.
Even if the membrane plug does not dislodge from the capsule, some high liquid uptake membrane plugs permit the osmotic agent to leak from the capsule because the membrane materials are biologically unstable. For instance, some semipermeable membranes having high permeability coefficients, such as organic polymer membranes, are unstable in biological environments and may degrade over time, permitting fluids, crystals, or powder within the interior of the capsule to leak to the environment of use. In some instances, the osmotic agent within the capsule may be harmful to the recipients of implantable delivery systems, especially if released as a bolus, i.e., all at once at a single location.
To ensure that the high liquid uptake membrane plug remains intact within the delivery system capsule and seals the interior of the capsule from the environment of use, some osmotic delivery systems use glues or adhesives with such high liquid uptake membrane plugs to prevent the capsule from leaking and to ensure that the membrane plug remains in place. Besides adding a manufacturing step and increasing costs, applying an adhesive to the membrane plugs may problematically affect the rate of permeation.
Still another problem associated with these high uptake membrane plugs is that the enclosure of the osmotic delivery system must be made sufficiently strong to withstand the greater forces exerted on the enclosure walls when the membrane plug expands radially.
Because of the above-identified problems associated with current osmotic delivery system membrane plugs, it is costly and particularly difficult to administer beneficial agents from osmotic delivery systems at different desired delivery rates. Known membrane plug designs control the permeation rate of the membrane and the beneficial agent delivery rate of the osmotic delivery system by selecting a different material membrane plug for each application requiring a particular beneficial agent administration rate. Additionally, current high liquid uptake membrane plugs may dislodge or leak, and may be unstable in biological environments, causing items in the interior of the delivery capsule to harmfully leak to the environment of use. These problems associated with current osmotic drug delivery systems having known membrane plugs have created a need for a solution.